Gui-Dong Shi, Xiao-Lei Zhang, Xin Cheng, Xu Wang, Bao-You Fan, Shen Liu, Yan Hao, Zhi-Jian Wei, Xian-Hu Zhou, Shi-Qing Feng
(Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China (mainland))
Med Sci Monit 2018; 24:8878-8890
Spinal cord injury (SCI) is a serious disease with high disability and mortality rates, with no effective therapeutic strategies available. In SCI, abnormal DNA methylation is considered to be associated with axonal regeneration and cell proliferation. However, the roles of key genes in potential molecular mechanisms of SCI are not clear.
MATERIAL AND METHODS: Subacute spinal cord injury models were established in Wistar rats. Histological observations and motor function assessments were performed separately. Whole-genome bisulfite sequencing (WGBS) was used to detect the methylation of genes. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID database. Protein–protein interaction (PPI) networks were analyzed by Cytoscape software.
RESULTS: After SCI, many cavities, areas of necrotic tissue, and many inflammatory cells were observed, and motor function scores were low. After the whole-genome bisulfite sequencing, approximately 96 DMGs were screened, of which 50 were hypermethylated genes and 46 were hypomethylated genes. KEGG pathway analysis highlighted the Axon Guidance pathway, Endocytosis pathway, T cell receptor signaling pathway, and Hippo signaling pathway. Expression patterns of hypermethylated genes and hypomethylated genes detected by qRT-PCR were the opposite of WGBS data, and the difference was significant.
CONCLUSIONS: Abnormal methylated genes and key signaling pathways involved in spinal cord injury were identified through histological observation, behavioral assessment, and bioinformatics analysis. This research can serve as a source of additional information to expand understanding of spinal cord-induced epigenetic changes.
Keywords: DNA Methylation, Epigenomics, Nerve Regeneration, Spinal Cord Injuries